Role of Neutrophil Activation in Anaphylaxis to Neuro-Muscular Blocking Agents
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Percentage of circulating activated neutrophils in the group case compared to that of the group of control.
研究概览
简要总结
In about 10% of preoperative anaphylactic reactions to Neuro-Muscular Blocking Agents (NMBA) (114 patients analyzed at the BICHAT Hospital), a classical mechanism (mast cell- and IgE-dependent) is not identified. The mechanisms underlying these atypical anaphylactic reactions are unknown. The investigators have developed at the Pasteur Institute a murine model of anaphylaxis in which neutrophils, IgG and Platelet Activating Factor (PAF) play predominant roles. In addition, preliminary results obtained at the BICHAT Hospital suggest the presence of specific IgG anti-quaternary ammonium in the sera of patients that had developed a shock to NMBA anesthesia, but not in controls exposed to NMBA anesthesia or in normal blood donors. Finally, the release of neutrophil extracellular traps (NETs), extracellular filaments made of DNA and histones, may contribute to respiratory symptoms HYPOTHESIS: Neutrophils are implicated in NMBA -induced anaphylactic reactions in humans. Activated by IgG-NMBA complexes, which aggregate IgG receptors, neutrophils release PAF and NETs that are implicated in the cardiac and respiratory distress during anaphylaxis. It is possible that the activation of neutrophils: 1) explains the clinical features of atypical anaphylactic reactions (non-IgE mediated), 2) participates also in part to classical anaphylactic reactions GENERAL OBJECTIVE: Compare the percentage of circulating activated neutrophils in a group of patients immediately following a NMBA -induced shock (case) to that of a group of patients exposed to NMBA during anesthesia without developing a shock (control).
SECONDARY OBJECTIVES:
A) the day of the shock, quantify and compare between case and controls, 1) the level of circulating anti-quaternary ammonium IgG by immuno fluorometry, 2) the expression of IgG receptors (FcR) on the surface of neutrophils by cytometry, 3) the levels of circulating PAF by mass spectrometry, 4) the amount of NETs by immunofluorescence.
B) 6 to 10 weeks after the shock perform, 1) cutaneous tests to NMBA, 2) a study of the capacity of stimulation of ex vivo neutrophils by IgG- NMBA complexes
详细描述
Case control study, with a 6,10 week follow-up on cases
Selection of cases :
Inclusion criteria: Any patient of age 18 and over:
Presenting with clinical signs compatible with a perioperative anaphylactic reaction to neuromuscular blocking drugs, whatever the grade of the anaphylactic reaction That was treated following the French Patient Management 2011 guidelines (cf. annex 5) Non inclusion criteria: patient dying during the anaphylactic shock
Selection of controls: One control for each case will be included. Controls will be recruited solely at the Hospital BICHAT. Controls should correspond to the following:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Percentage of circulating activated neutrophils in the group case compared to that of the group of control.
时间窗: 30min post-anaphylactic shock
This measure will be based on the intensity of expression of the activation marker CD62L (L-selectin) by blood neutrophils using flow cytometry. Our preliminary data indicate that the Mean Fluorescence Intensity (MFI) of CD62L is \>450 when considering " non-activated " neutrophils, and CD62L(MFI)\<300 when considering " activated " neutrophils.
次要结局
- Levels of anti-quaternary ammonium specific IgG in the plasma(30min post-anaphylactic shock)
- Ex vivo activation capacity of blood neutrophils in the presence of neuromuscular blocking drug-IgG immune complexes(30min post-anaphylactic shock)
- Presence of Neutrophil Extracellular Traps in the bronchial aspiration fluid of "cases"(30min post-anaphylactic shock)